Loss of C2 Domain Protein (C2CD5) Alters Hypothalamic Mitochondrial Trafficking, Structure, and Function

Gavini, Chaitanya K.; White, Chelsea R.; Mansuy‐Aubert, Virginie; Aubert, Grégory

doi:10.1159/000517273

Cited by 4 publications

(2 citation statements)

References 57 publications

(116 reference statements)

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“…A Seahorse XFe96 Analyzer (Agilent, California, USA) was used to measure oxygen consumption rate (OCR) [ 46 – 48 ] of macrophages (seeding density 100,000 cells/well) treated with oxLDL and GW3965 as described above. Briefly, 1 h before the assay, culture media was aspirated from the cells in the plate and Seahorse XF assay media supplemented with 20 mM glucose and 2 mM glutamine was applied and equilibrated in a CO 2 free incubator.…”

Section: Methodsmentioning

confidence: 99%

LXR agonist improves peripheral neuropathy and modifies PNS immune cells in aged mice

Gavini

Elshareif

Aubert

et al. 2022

J Neuroinflammation

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Background Peripheral neuropathy is a common and progressive disorder in the elderly that interferes with daily activities. It is of importance to find efficient treatments to treat or delay this age-related neurodegeneration. Silencing macrophages by reducing foamy macrophages showed significant improvement of age-related degenerative changes in peripheral nerves of aged mice. We previously demonstrated that activation of the cholesterol sensor Liver X receptor (LXR) with the potent agonist, GW3965, alleviates pain in a diet-induced obesity model. We sought to test whether LXR activation may improve neuropathy in aged mice. Methods 21-month-old mice were treated with GW3965 (25 mg/Kg body weight) for 3 months while testing for mechanical allodynia and thermal hyperalgesia. At termination, flow cytometry was used to profile dorsal root ganglia and sciatic nerve cells. Immune cells were sorted and analyzed for cholesterol and gene expression. Nerve fibers of the skin from the paws were analyzed. Some human sural nerves were also evaluated. Comparisons were made using either t test or one-way ANOVA. Results Treatment with GW3965 prevented the development of mechanical hypersensitivity and thermal hyperalgesia over time in aged mice. We also observed change in polarization and cholesterol content of sciatic nerve macrophages accompanied by a significant increase in nerve fibers of the skin. Conclusions These results suggest that activation of the LXR may delay the PNS aging by modifying nerve-immune cell lipid content. Our study provides new potential targets to treat or delay neuropathy during aging.

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Section: Methodsmentioning

confidence: 99%

LXR agonist improves peripheral neuropathy and modifies PNS immune cells in aged mice

Gavini

Elshareif

Aubert

et al. 2022

J Neuroinflammation

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“…Concerning the cytoskeleton function, there is increasing interest regarding its involvement in organelle transport, in particular mitochondria. Light microscopy with the use of fluorescent probes can evidence how mitochondria move along axons [ 105 , 106 , 107 ]. The fluorescent probes are inserted in the cells under investigation by transfection or MitoTracker dye, an easy and ready-to-use probe that accumulates in mitochondria through membrane potential.…”

Section: Microscopic Approaches To Visualize and Assess Cytoskeleton ...mentioning

confidence: 99%

Neurons: The Interplay between Cytoskeleton, Ion Channels/Transporters and Mitochondria

Alberti

Semperboni

Cavaletti

et al. 2022

Cells

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Neurons are permanent cells whose key feature is information transmission via chemical and electrical signals. Therefore, a finely tuned homeostasis is necessary to maintain function and preserve neuronal lifelong survival. The cytoskeleton, and in particular microtubules, are far from being inert actors in the maintenance of this complex cellular equilibrium, and they participate in the mobilization of molecular cargos and organelles, thus influencing neuronal migration, neuritis growth and synaptic transmission. Notably, alterations of cytoskeletal dynamics have been linked to alterations of neuronal excitability. In this review, we discuss the characteristics of the neuronal cytoskeleton and provide insights into alterations of this component leading to human diseases, addressing how these might affect excitability/synaptic activity, as well as neuronal functioning. We also provide an overview of the microscopic approaches to visualize and assess the cytoskeleton, with a specific focus on mitochondrial trafficking.

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MC4R in Central and Peripheral Systems

Wei

Jia

et al. 2023

Advanced Biology

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Obesity has emerged as a critical and urgent health burden during the current global pandemic. Among multiple genetic causes, melanocortin receptor‐4 (MC4R), involved in food intake and energy metabolism regulation through various signaling pathways, has been reported to be the lead genetic factor in severe and early onset obesity and hyperphagia disorders. Most previous studies have illustrated the roles of MC4R signaling in energy intake versus expenditure in the central system, while some evidence indicates that MC4R is also expressed in peripheral systems, such as the gut and endocrine organs. However, its physiopathological function remains poorly defined. This review aims to depict the central and peripheral roles of MC4R in energy metabolism and endocrine hormone homeostasis, the diversity of phenotypes, biased downstream signaling caused by distinct MC4R mutations, and current drug development targeting the receptor.

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Loss of C2 Domain Protein (C2CD5) Alters Hypothalamic Mitochondrial Trafficking, Structure, and Function

Cited by 4 publications

References 57 publications

LXR agonist improves peripheral neuropathy and modifies PNS immune cells in aged mice

LXR agonist improves peripheral neuropathy and modifies PNS immune cells in aged mice

Neurons: The Interplay between Cytoskeleton, Ion Channels/Transporters and Mitochondria

MC4R in Central and Peripheral Systems

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